Drug Penetration Into Bone After Repeated Oral Administration of Debio 1450 to Patients Undergoing Hip Replacement Surgery

NCT02726438 | Completed Phase 1

• 2 other identifiers: Debio 1450-108226488
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 2

Brief Summary

Debio 1450 is being developed for the treatment of staph (staphylococcal) infections. How fast and completely an antibiotic penetrates into bone is used to determine how effective it might be to treat infections related to bones or joints. Since bone has fewer blood vessels than other tissue (for example lung tissue or the skin), drugs have a harder time getting into them. It is important to find out how much of the antibiotic can get into the bone to help patients with bone infections.

Conditions

Bone Diseases, Infectious

Outcome Measures

Primary Outcomes (1)

• Bone to plasma ratio for Debio 1452 (the Debio 1450 active moiety)

  Bone/bone marrow/soft tissue/synovial fluid samples will be collected during surgery; time of resection will be used to calculate the elapsed time after last dosing.

  at pre-last dose (predose of the 3rd dose), at 0.5, 1, 2, 3, 5, 8, 12 hours post-last dose (Dose 3) and at the time of bone resection (surgery); only at the time of bone resection for the calibration participant

Secondary Outcomes (4)

• Plasma ratios for Debio 1452

  at pre-last dose (predose of the 3rd dose), at 0.5, 1, 2, 3, 5, 8, 12 hours post-last dose (Dose 3) and at the time of bone resection (surgery); only at the time of bone resection for the calibration participant

• Area under the curve at steady state (AUCτ) of Debio 1452

  at pre-last dose (predose of the 3rd dose), at 0.5, 1, 2, 3, 5, 8, 12 hours post-last dose (Dose 3) and at the time of bone resection (surgery); only at the time of bone resection for the calibration participant

• Maximum observed plasma concentration (Cmax) of Debio 1452

  at pre-last dose (predose of the 3rd dose), at 0.5, 1, 2, 3, 5, 8, 12 hours post-last dose (Dose 3) and at the time of bone resection (surgery); only at the time of bone resection for the calibration participant

• Measured concentration at the end of a dosing interval at steady state (Ctrough) of Debio 1452

  at pre-last dose (predose of the 3rd dose), at 0.5, 1, 2, 3, 5, 8, 12 hours post-last dose (Dose 3) and at the time of bone resection (surgery); only at the time of bone resection for the calibration participant

Study Arms (2)

Debio 1450

EXPERIMENTAL

Participants will receive 3 oral administrations of Debio 1450 at a dose of 240 mg approximately 12 hours apart. The last dose should be given approximately 2, 4, 6 or 12 hours prior to surgery with 3 patients each to be dosed at each of these time points. If the surgery is delayed by more than 12 hours postdose, the patients could receive up to 2 additional administrations (approximately 12 hours apart) to ensure that the last dose is administered between 2 and 12 hours before the surgery.

Drug: Debio 1450

Calibration

NO INTERVENTION

A single participant will not receive the study drug, providing data to be used as calibration.

Interventions

Debio 1450 DRUG

Debio 1450, 40 mg, powder for oral solution, for reconstitution in 5% dextrose in water.

Debio 1450

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Meets protocol-specified criteria for qualification and contraception
• Is willing and able to comply with restrictions related to food, drink and medications
• Voluntarily consents to participate and provides written informed consent prior to any protocol-specific procedures

You may not qualify if:

• Has history or current use of over-the-counter medications, dietary supplements, or drugs (including nicotine and alcohol) outside protocol-specified parameters
• Has signs, symptoms or history of any condition that, per protocol or in the opinion of the investigator, might compromise:
• the safety or well-being of the participant or study staff;
• the safety or well-being of the participant's offspring (such as through pregnancy or breast-feeding);
• the analysis of results

Sponsors & Collaborators

• Debiopharm International SA: lead

Study Sites (2)

eStudySite

La Mesa, California, 91941, United States

Location

Mercury St Medical Group, PLLC

Butte, Montana, 59701, United States

Location

Related Publications (1)

• Menetrey A, Janin A, Pullman J, Overcash JS, Haouala A, Leylavergne F, Turbe L, Wittke F, Nicolas-Metral V. Bone and Joint Tissue Penetration of the Staphylococcus-Selective Antibiotic Afabicin in Patients Undergoing Elective Hip Replacement Surgery. Antimicrob Agents Chemother. 2019 Feb 26;63(3):e01669-18. doi: 10.1128/AAC.01669-18. Print 2019 Mar.

  PMID: 30559136 DERIVED

MeSH Terms

Conditions

Bone Diseases, Infectious

Interventions

afabicin

Condition Hierarchy (Ancestors)

Infections; Bone Diseases; Musculoskeletal Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 29, 2016
• First Posted: April 1, 2016
• Study Start: April 1, 2016
• Primary Completion: June 1, 2017
• Study Completion: June 1, 2017
• Last Updated: October 18, 2017

Record last verified: 2017-10

Locations

US (2)